Genetic markers for prognosis of antifolate treatment efficacy

Abstract

Methods and kits for predicting the efficacy of antifolate (e.g., methotrexate) treatment of rheumatoid arthritis by detecting polymorphisms, particularly single nucleotide polymorphisms, in adenosine pathway genes.

1. A method for determining clinical responsiveness to methotrexate therapy in a human subject afflicted with, or at risk of developing, rheumatoid arthritis comprising detecting in a nucleic acid sample from the subject the presence of a 94A>C polymorphism in the inosine triphosphate pyrophosphatase (ITPA) gene, wherein the presence of said polymorphism is indicative of clinical responsiveness to said methotrexate therapy. 
     
     
       2. The method according to  claim 1 , wherein said methotrexate responsiveness is measured as a disease activity score (DAS) less than or equal to 2.4. 
     
     
       3. The method according to  claim 1 , wherein the polymorphism is detected by microarray analysis, DNA sequencing or allele specific PCR techniques. 
     
     
       4. The method of  claim 1 , further comprising selecting or adjusting said methotrexate therapy depending upon the results of said detecting. 
     
     
       5. The method of  claim 4 , wherein said selected or adjusted methotrexate therapy is methotrexate monotherapy, methotrexate combination therapy, or methotrexate biologic therapy. 
     
     
       6. The method of  claim 1  further comprising detecting the presence of at least one polymorphism selected from the group consisting of a 34C>T polymorphism in the adenosine monophosphate deaminase (AMPD1) gene, a 2756A>G polymorphism in the methionine synthase (MTR) gene, and a 66A>G polymorphism in the methionine synthase reductase (MTRR) gene, wherein the presence of said polymorphisms is indicative of clinical responsiveness to said antifolate therapy.